gpr50 interacts with tip60 to modulate glucocorticoid receptor signallinggpr50与tip60糖皮质激素受体信号调节.pdfVIP

GPR50 Interacts with TIP60 to Modulate Glucocorticoid Receptor Signalling Jian Li, Laura E. Hand, Qing-Jun Meng, Andrew S. I. Loudon*, David A. Bechtold* Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom Abstract GPR50 is an orphan G-protein coupled receptor most closely related to the melatonin receptors. The physiological function of GPR50 remains unclear, although our previous studies implicate the receptor in energy homeostasis. Here, we reveal a role for GPR50 as a signalling partner and modulator of the transcriptional co-activator TIP60. This interaction was identified in a yeast-two-hybrid screen, and confirmed by co-immunoprecipitation and co-localisation of TIP60 and GPR50 in HEK293 cells. Co-expression with TIP60 increased perinuclear localisation of full length GPR50, and resulted in nuclear translocation of the cytoplasmic tail of the receptor, suggesting a functional interaction of the two proteins. We further demonstrate that GPR50 can enhance TIP60-coactiavtion of glucocorticoid receptor (GR) signalling. In line with in vitro results, repression of pituitary Pomc expression, and induction of gluconeogenic genes in liver in response to the GR agonist, dexamethasone was attenuated in Gpr502/ 2 mice. These results identify a novel role for GPR50 in glucocorticoid receptor signalling through interaction with TIP60. Citation: Li J, Hand LE, Meng Q-J, Loudon ASI, Bechtold DA (2011) GPR50 Interacts with TIP60 to Modulate Glucocorticoid Receptor Signalling. PLoS ONE 6(8): e23725. doi:10.1371/journal.pone.0023725 ´ Editor: Vincent Laudet, Ecole Normale Superieure de Lyon, France Received February 2, 2011; Accepted July 26, 2011; Published August 17, 2011 Copyright: 2011 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permit